Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Ahn, Jae Eun; Cloyd, James C.; Brundage, Richard C.; Marino, Susan E.; Conway, Jeannine M.; Ramsay, R. Eugene; White, James R.; Musib, Luna; Rarick, John O.; Leppik, Ilo E.

doi:10.1212/01.wnl.0000316392.55784.57

Cited by 32 publications

(25 citation statements)

References 37 publications

(59 reference statements)

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“…Our findings showed that the plasma concentrationtime curve for phenytoin was fitted using a 1-compartment open model with linear absorption and MichaelisMenten elimination that corroborated previous studies [17,18]. We estimated the V max and K m parameters in our population, which is very critical for personalizing the phenytoin dosage.…”

Section: Discussionsupporting

confidence: 88%

Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients

et al. 2019

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Objective: This study aimed to assess the population pharmacokinetics of phenytoin in Saudi patients and identify factors affecting therapeutic parameters. Method: A retrospective chart review was performed at King Saud University Medical City on patients treated with oral phenytoin. We used Monolix 4.4. for population pharmacokinetic modeling. A base model was developed to investigate several covariates, including age, gender, weight, total daily dose (TTD), and liver function test results. Results: The analysis included a total of 81 phenytoin plasma concentrations from 43 patients (70% male). Patients’ mean (± SD) age was 41 (±18.7) years and body weight was 65.4 (±17.7) kg. The patients received a phenytoin TDD of 330.5 (±104.5) mg/day, resulting in a trough concentration of 11.2 (±10.3) mg/L. The data were sufficiently described by the one-compartment open model with linear absorption and nonlinear elimination processes. Average parameter estimates for phenytoin volume of distribution (V), maximal elimination rate (V_max), and Michaelis-Menten constant (K_m) were 0.61 L/h/kg, 6.12 mg/kg/day, and 5.33 mg/L, respectively. The most significant covariates on phenytoin V_max and K_m were the age and body weight of the patients, along with valproic acid (VPA) cotherapy. Conclusion: The population pharmacokinetic model of phenytoin in Saudi patients found significant interindividual variability between subjects, which was affected by the patients’ age, body weight, and VPA cotherapy as the most significant covariates on phenytoin V_max and K_m. To provide guidance in drug dosage decisions, further studies are required to evaluate all factors that may potentially influence the pharmacokinetics of phenytoin.

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Section: Discussionsupporting

confidence: 88%

Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients

et al. 2019

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“…Data from pharmacokinetic analysis in old patients taking phenytoin revealed aging is associated with a gradual decline in AED clearance 34 . Furthermore, as serum albumin level falls gradually with each decade of age 35 , relatively lower phenytoin doses and lower plasma concentrations can be adequate for satisfactory seizure control in elderly patients 36,37 . The therapeutic window needs to be narrowed down in elderly patients.…”

Section: Pharmacological Changes Of Aeds In the Elderlymentioning

confidence: 99%

Epilepsy in the Elderly

Chen

Cheng

Jou

2012

International Journal of Gerontology

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s u m m a r y Elderly people are the largest and continuously fastest growing population among patients with epilepsy. Elderly patients with epilepsy are very different from other age groups in many respects and clinicians shouldn't treat them in the same way as younger adults. Accurate diagnosis of epilepsy in the elderly is much more difficult and atypical manifestations and misdiagnoses are certainly not the exception. Syncope is probably the most important differential diagnosis. High clinical suspicion and proper investigation are the best tools for prompt diagnosis. Etiologies of late-onset epilepsy are mainly symptomatic and cerebrovascular diseases are the most common causes in this age group, followed by degenerative diseases such as Alzheimer's disease. It is appropriate to consider starting antiepileptic drug (AED) treatment at the first-ever seizure in elderly patients who have remote symptomatic causes such as stroke and dementia. According to the high recurrence rate of seizure and the good response to AEDs in elderly patients, the proper choice from various AEDs for seizure control is very important. Decisionmaking for AED choice depends on many different factors, including pharmacological properties, efficacy, tolerability from side effects, drug interactions, and medical comorbidities. The newer AEDs with lesser adverse effects and fewer drug interactions appear to be reasonable treatment options for elderly patients. However, more evidence from clinical trials in this specific age group is warranted.

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“…Because of the complexity of confounding variables and the lack of correlation between simple measures of liver function and drug metabolism, the effect of age on hepatic drug metabolism remains largely unknown [21]. Interestingly, genetic determinants of hepatic isoenzymes may be more important than age in determining a person's clearance [22].…”

Section: Choosing the Right Aedmentioning

confidence: 99%

“…A recent study suggested that metabolism does not decrease greatly with age in healthy elderly. Using stable-labeled (nonradioactive) phenytoin to very precisely measure the phenytoin clearance, one study found that advancing age was not as much of a factor as had been previously reported [32]. A range of 5-15 mg/L total may be more appropriate as a therapeutic range for the elderly due to abnormal protein binding [33].…”

Section: Phenytoinmentioning

confidence: 99%

Medical Management of Seizures in Cerebrovascular Disorders

Menon

Leppik

2015

Seizures in Cerebrovascular Disorders

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Cerebrovascular disorders are one of the most common identifiable causes of epilepsy, especially in the elderly [1]. Seizures after a stroke can occur early, within 7-14 days [2-6], or late, after 14 days [7][8][9][10]. Early seizures do not necessarily progress to epilepsy, but may result in increased morbidity and mortality. Reports vary considerably regarding the incidence of single seizures and epilepsy after a stroke. In adults younger than 50 years of age, 12.7 % with ischemic strokes and 25.6 % with intracranial hemorrhage developed epilepsy. This study used the more recent definition of epilepsy, which is the occurrence of a single seizure associated with an enduring condition associated with epilepsy. Another large study reported the occurrence of seizures in 168 (8.9 %) of 1897 persons following an ischemic stroke and 28 (10.6 %) of 265 after a hemorrhagic stroke [4]. Most seizures occurred within 2 years of the stroke.A critical question addressing the issue of treatment is the occurrence of a second seizure after a single seizure. Unfortunately, this is a difficult question to answer from the literature. Many physicians initiate treatment with antiepileptic drugs (AEDs) following a single seizure because of the perception that there is a high risk of additional seizures in the context of stroke and seizure. Thus, reports of recurrent seizures are confounded with treatment, and it is difficult to establish the risk of epilepsy as defined by two or more unprovoked seizures. In one study by Arntz, 75 % of persons with an ischemic stroke and 80 % with a hemorrhagic stroke were

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Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Cited by 32 publications

References 37 publications

Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients

Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients

Epilepsy in the Elderly

Medical Management of Seizures in Cerebrovascular Disorders

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